Cryptococcosis is an increasingly frequent and usually fatal opportunistic infection of patients with the acquired immunodeficiency syndrome (AIDS). The etiology of cryptococcosis in patients with AIDS and in most patients without AIDS is Cryptococcus neoformans var. neoformans serotype A. Preliminary studies have established that strains of C. neoformans serotype a vary in pathobiologic properties. Strains of C. neoformans serotype A from patients with AIDS and from patients without AIDS will be compared with previously characterized strains and mutants. The proposed biological and biochemcial studies will elucidate the determinant(s) of pathogenicity. Strains will be compared for lethality for animals, susceptibility to phagocytosis and intracellular killing, and the size, structure, and biologic properties of the capsular polysaccharides (CPS). The initial defense mechanism against cryptococcosis, the interaction of yeast cells with alveolar macrophages, will be scrutinized in vitro. The antiphagocytic activity, binding to nonencapsulated yeast cells, and the effects on complement activation and leukocyte chemotaxis of CPS from each strain will be evaluated and correlated with its source and virulence. These biologic studies will involve leukocytes and serum from normal and infected Lewis rats. Composition and structure of the CPS from each strain will be analyzed by 13C nuclear magnetic resonance spectroscopy and other techniques in collaboration with Dr. Robert Cherniak.